Abnormal Grey Matter Arteriolar Cerebral Blood Volume in Schizophrenia Measured With 3D Inflow-Based Vascular-Space-Occupancy MRI at 7T

Abstract

Metabolic dysfunction and microvascular abnormality may contribute to the pathogenesis of schizophrenia. Most previous studies of cerebral perfusion in schizophrenia measured total cerebral blood volume (CBV) and cerebral blood flow (CBF) in the brain, which reflect the ensemble signal from the arteriolar, capillary, and venular compartments of the microvasculature. As the arterioles are the most actively regulated blood vessels among these compartments, they may be the most sensitive component of the microvasculature to metabolic disturbances. In this study, we adopted the inflow-based vascular-space-occupancy (iVASO) MRI approach to investigate alterations in the volume of small arterial (pial) and arteriolar vessels (arteriolar cerebral blood volume [CBVa]) in the brain of schizophrenia patients. The iVASO approach was extended to 3-dimensional (3D) whole brain coverage, and CBVa was measured in the brains of 12 schizophrenia patients and 12 matched controls at ultra-high magnetic field (7T). Significant reduction in grey matter (GM) CBVa was found in multiple areas across the whole brain in patients (relative changes of 14%-51% and effect sizes of 0.7-2.3). GM CBVa values in several regions in the temporal cortex showed significant negative correlations with disease duration in patients. GM CBVa increase was also found in a few brain regions. Our results imply that microvascular abnormality may play a role in schizophrenia, and suggest GM CBVa as a potential marker for the disease. Further investigation is needed to elucidate whether such effects are due to primary vascular impairment or secondary to other causes, such as metabolic dysfunction.

Association of sFlt-1 and worsening psychopathology in relatives at high risk for psychosis: A longitudinal study

“…Due to advances in retinal and neuroimaging, it is now possible to study arteriolar, venular, and vasoregulatory mechanisms in vivo and there are a few studies implicating microvasculature disruption in patients with schizophrenia (Allen et al, 2016; Hua et al, 2016; Meier et al, 2013). Developmentally, a large longitudinal study showed that second trimester maternal angiogenesis levels were associated with narrower childhood retinal arteriolar caliber, but not with retinal venular caliber (Gishti et al, 2015).…”

“…Microvascular abnormality may contribute to the pathophysiology of psychotic disorders, as evidenced by capillary ultra-structural damage, reduced blood flow, altered glucose metabolism, retinal microvascular abnormalities, uncoupling of cerebral blood flow/volume, and arteriolar cerebral blood volume reductions in SZ (Hua et al, 2016; Meier et al, 2013; Talati et al, 2015; Uranova et al, 2010; Uranova, 2013), and investigating angiogenic pathways may provide a novel biological framework for understanding these phenotypes (Lopes et al, 2015). Angiogenesis involves a balance between pro- and anti-angiogenic factors and can result in various pathological conditions (Wu et al, 2010).…”

Emerging links between cerebrovascular and neurodegenerative diseases—a special role for pericytes

“…BBB dysfunction was likewise observed in a boxer suffering from chronic traumatic encephalopathy [127]. In addition to the neurological problems, an aberrant microvasculature as well as abnormal CBF is observed in schizophrenia [128][129][130]. The cause of schizophrenia is not well-understood but may involve disturbed dopamine and NMDA receptor signaling.…”

Microvascular anomaly conditions in psychiatric disease. Schizophrenia – angiogenesis connection

“…Other regions, where hypoperfusion in SZ has been extensively documented, include middle and anterior cingulate, temporal and parietal regions (Ojeda et al, 2002; Schultz et al, 2002; Yucel et al, 2002) and thalamus (Clark et al, 2001). More recently, MRI based investigation of alterations in the volume of small arterial (pial) and arteriolar vessels in brains of individuals with SZ suggested that microvascular abnormalities maybe more widespread across the entire brain (Hua et al, 2016). Reduced CBF has been also associated with psychotic symptoms.…”